PROJECT SUMMARY We are proposing a NIDA Research Center of Excellence (P50) entitled, Center for Adolescent Reward, Rhythms and Sleep (CARRS). Adolescence is a vulnerable time for substance abuse. This risk reflects the heightened reward system of adolescence, which is found regardless of cultural upbringing or home environment, relative to both adults and children. In addition, genetic, social and environmental factors influence the amount of sleep and circadian rhythm misalignment experienced by the adolescent brain. The goal of CARRS is to integrate human and rodent studies to understand the impact of adolescent sleep and circadian rhythm changes (both biologically and environmentally induced) on reward circuitry and substance use (SU)- relevant outcomes. We will use experimental manipulations to further examine how sleep and circadian rhythms affect reward function and SU-related outcomes, with the ultimate goal of developing novel prevention or intervention strategies. Late sleep timing, short sleep duration and circadian misalignment are associated with increased substance use in teenagers and young adults. The central hypothesis of the Center is that adolescent development acts on underlying sleep and circadian traits to modify homeostatic sleep drive, circadian phase, and circadian alignment, which in turn impact cortico-limbic functions critical to substance use risk (e.g., reward and cognitive control). We further hypothesize that specific manipulations of sleep and circadian rhythms during adolescence will affect reward responsivity and cognitive control in either positive or negative directions. These manipulations will provide experimental support for our model, and proof of concept for novel clinical interventions to reduce the risk of substance use disorders. In turn, abuse of drugs will also impact the circadian, reward and sleep systems, creating a vicious cycle. Interventions that help stabilize the circadian and sleep systems, or reduce the damage done by these disruptions, may be protective against substance abuse in vulnerable individuals. The goals of the center are to 1) Determine the role of sleep and circadian rhythms in reward sensitivity and substance use (SU) in adolescence. 2) Conduct translational research aimed at the development of interventions to reduce risk in at-risk individuals. 3) Partner with other Centers and the addiction research community to inform and complement ongoing research. 4) Provide training and education on sleep, circadian rhythms, and substance use.